Table 2.

Summary of types of analyses and exposure metrics to consider

Exposure metric	Analysis	Endpoints
Single exposure metric representing the course of treatment or exposure to the time of the event: *Ctrough, *Cavg, *AUCss, *Cmax, Cobs, *time above a treshold concentration	KM Curves, Cox proportional hazards Logistic regression Empirical myelosuppression models	PFS, EFS, OS ORR, CR, MRD, AE grades, Myelosuppression grades
Longitudinal exposure (time-varying exposure): *C(t), *Ctrough(t), *Cave(t)	Multi-state models Parametric time-to-event Markov models Tumor growth dynamics Time-course of myelosuppression Disease progression models	SLD-TTE PFS, EFS, OS, AE events SLD neutropenia, lymphopenia, anemia, and thrombocytopenia, Time-course of biomarkers as surrogates of efficacy

AE adverse event, AUC_ss area under the curve at steady-state, CR complete response, C_avg average concentration calculated as the ratio of cumulative AUC over the timeframe for the cumulative exposure, C_max maximum concentration, C_obs observed concentration, C_trough concentration prior to dose, EFS event free survival, KM Kaplan–Meier, MRD minimal residual disease, ORR objective response rate, OS overall survival, PFS progression free survival, SLD sum of the longest diameter, TTE time-to-event

*Model predicted/estimated exposure metrics